PHARMACEUTICAL COMPOSITION FOR POORLY SOLUBLE DRUGS

• US 20110014282A1
• Filed: 02/27/2009
• Published: 01/20/2011
• Est. Priority Date: 02/28/2008
• Status: Abandoned Application

• Current Assignee: BIAL Portela & Ca, SA
• Original Assignee: BIAL Portela & Ca, SA
• Inventors: de Vasconcelos, Teofilo Cardoso
• Application Number:
  US12/920,025
• Publication Number:
  US 20110014282A1
• Time in Patent Office: Days
• US Class Current: 424/452
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/12 : Antihypertensives

Abstract

A pharmaceutical composition containing a solid dispersion of a poorly soluble active pharmaceutical ingredient, an amorphous carrier and a surfactant.

Claims

1. A solid dosage form for release of a poorly soluble active pharmaceutical ingredient (API), the solid dosage form comprising a solid dispersion, the solid dispersion comprising a active pharmaceutical ingredient belonging to BCS Class II, an amorphous carrier and a surfactant, wherein the amount of surfactant is from 0.5 to 30% of the total weight of the solid dispersion, and wherein at least 30% of the active pharmaceutical ingredient is in an amorphous form.

2. A solid dosage form as claimed in claim 1 wherein the dosage form is for fast release of the API.

3. A solid dosage form as claimed in claim 1 or claim 2 wherein, when the dosage form is placed in a volume of less than 1000 ml of water, more than 85% of the API dissolves in less than 60 minutes.

4. A solid dosage form as claimed in claim 3 wherein, when the dosage form is placed in a volume of less than 1000 ml of water, more than 85% of the API dissolves in less than 30 minutes.

5. A solid dosage form as claimed in claim 1 wherein the dosage form is for sustained release of the API.

6. A solid dosage form as claimed in claim 5 wherein, when the dosage form is placed in a volume of less than 1000 ml of water, more than 85% of the API dissolves in less than 12 hours.

7. A solid dosage form as claimed in any preceding claim wherein the dosage form is a capsule formulation, the solid dispersion being contained within an outer casing of a pharmaceutically acceptable material.

8. A solid dosage form as claimed in any of claims 1 to 6 wherein the dosage form is a compressed dosage form.

9. A solid dosage form as claimed in claim 8 wherein the dosage form is a tablet.

10. A solid dosage form as claimed in claim 8 or claim 9 wherein the dosage form has a resistance to a crushing force of from 0.1 to 300 N.

11. A solid dosage form as claimed in claim 10 wherein the composition has a resistance to a crushing force of from 20 to 200 N.

12. A solid dosage form as claimed in any preceding claim wherein the solid dispersion does not contain a superdisintegrant.

13. A solid dosage form as claimed in any preceding claim wherein the dosage form does not contain a superdisintegrant.

14. A solid dosage form as claimed in any preceding claim wherein at least 50% of the active pharmaceutical ingredient is in an amorphous form.

15. A solid dosage form as claimed in claim 14 wherein at least 75% of the active pharmaceutical ingredient is in an amorphous form.

16. A solid dosage form as claimed in claim 15 wherein at least 90% of the active pharmaceutical ingredient is in an amorphous form.

17. A solid dosage form as claimed in any preceding claim wherein the amount of surfactant is from 2 to less than 24% of the total weight of the solid dispersion.

18. A solid dosage form as claimed in claim 17 wherein the amount of surfactant is from 2 to 16% of the total weight of the solid dispersion.

19. A solid dosage form as claimed in claim 18 wherein the amount of surfactant is from 2 to 10% of the total weight of the solid dispersion.

20. A solid dosage form as claimed in claim 19 wherein the amount of surfactant is from 4 to 8% of the total weight of the solid dispersion.

21. A solid dosage form as claimed in any preceding claim, wherein the surfactant is selected from inulin (inutec), mono-, di- and triglycerides of behenic acid (compritol 888 ATO), glycerol and PEG1500 esters of long fatty acids (gelucire), sodium docusate, self emulsifying glyceryl monooleate (tegin), cetrimide, polyoxyethylene alkyl ethers (brij), polyoxyethylene castor oil derivates (simusol), polyoxyethylene stearates (Hadag, Kessco), sorbitan esters (span), poloxamer (pluronics), sodium lauryl sulphate and polysorbates.

22. A solid dosage form as claimed in any of claims 1 to 20 wherein the surfactant is a non-ionic surfactant.

23. A solid dosage form as claimed in claim 22, wherein the surfactant is polysorbate 80.

24. A solid dosage form as claimed in any preceding claim wherein the active pharmaceutical ingredient is a drug which is active on the central nervous system.

25. A solid dosage form as claimed in claim 24 wherein the active pharmaceutical ingredient is selected from analgesics, antipyretics, headache drugs, antidepressants, muscular relaxants, antiepileptics, anticonvulsive drugs, antiparkinsonian drugs, antiemetics, anxiolytics, drugs used in the treatment of affective disorders such as bipolar disorder, antipsychotics and anti-Alzheimer drugs.

26. A solid dosage form as claimed in any of claims 1 to 23 wherein the active pharmaceutical ingredient is a COMT inhibitor, a FAAH inhibitor, a dopamine β

hydroxylase inhibitor or a sodium channel antagonist.

27. A solid dosage form as claimed any of claims 1 to 23 wherein the active pharmaceutical ingredient is 5-[3-(2,5-dichloro-4,6-dimethyl-1-oxy-pyridine-3-yl)-[1,2,4]oxadiazol-5-yl]-3-nitrobenzene-1,2-diol.

28. A solid dosage form as claimed in any of claims 1 to 23 wherein the active pharmaceutical ingredient is 5-[3-(2,5-dichloro-4,6-dimethylpyridine-3-yl)-[1,2,4]oxadiazol-5-yl]-3-nitrobenzene-1,2-diol.

29. A solid dosage form as claimed in one of claims 1 to 23 wherein the active pharmaceutical ingredient is a cardiovascular active drug.

30. A solid dosage form as claimed in claim 29 wherein the active pharmaceutical ingredient is selected from cardiotonic drugs, antiarrhythmics, sympathomimetics, anti-hypertensives, vasodilators and cholesterol lowering drugs.

31. A solid dosage form as claimed in any preceding claim wherein the amorphous carrier is a polymer.

32. A solid dosage form as claimed in claim 31 wherein the polymer is selected from the group consisting of cellulose derivatives, starch derivatives, polyethyleneglycol, polymethylacrylate, carbomer, polyvinyl acetate, povidone, crospovidone, D-alpha-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS 1000) and vinylpyrrolidone/vinylacetate copolymer (copovidone, PVP VA64).

33. A solid dosage form as claimed in claim 32 wherein the cellulose derivative is selected from the group consisting of hydroxylpropylmethylcellulose, ethylcellulose, methylcellulose, hydroxypropylcellulose and hypromellose acetate succinate.

34. A solid dosage form as claimed in claim 32 wherein the starch derivative is a cyclodextrin.

35. A solid dosage form as claimed in claim 32 wherein the polyethyleneglycol (PEG) is a PEG having a molecular mass from 3000 g/mol to 20000 g/mol.

36. A solid dosage form as claimed in claim 35 wherein the polyethyleneglycol is PEG6000.

37. A solid dosage form as claimed in any preceding claim wherein the active pharmaceutical ingredient and the amorphous carrier are present in a ratio of 1 part API to from 0.5 to 1.5 parts carrier.

38. A solid dosage form as claimed in claim 37 wherein the active pharmaceutical ingredient and the amorphous carrier are present in a ratio of 1:

1.

39. A solid dosage form as claimed in any preceding claim wherein the ratio of the active pharmaceutical ingredient to amorphous carrier to surfactant is from 25 to 65:

from 25 to 65;

from 0.5 to 30.

40. A solid dosage form as claimed in claim 39 wherein the ratio of the active pharmaceutical ingredient to amorphous carrier to surfactant is from 35 to 49.7:

from 35 to 49.7;

from 0.6 to 24.

41. A solid dosage form as claimed in claim 40 wherein the ratio of the active pharmaceutical ingredient to amorphous carrier to surfactant is from 45 to 49:

from 45 to 49;

from 2 to 10.

42. A solid dosage form as claimed in claim 41 wherein the ratio of the active pharmaceutical ingredient to amorphous carrier to surfactant is from 46 to 48:

from 46 to 48;

from 4 to 8.

43. A solid dosage form as claimed in any preceding claim, wherein the composition comprises a filler.

44. A solid dosage form as claimed in any preceding claim, wherein the composition further comprises a lubricant.

45. A solid dosage form as claimed in any preceding claim, wherein the active pharmaceutical ingredient is not soluble in 250 ml of water-based buffers with a pH between 1-7.5.